Secondary B cell repertoire diversification occurs by somatic hypermutation (SHM) in germinal centers following Ag stimulation. In SHM, activation-induced cytidine deaminase mutates the V region of the Ig genes to increase the affinity of Abs. Although SHM acts primarily at Ig loci, low levels of off-target mutation can result in oncogenic DNA damage, illustrating the importance of understandin...

We generalize Deitchman’s guerrilla warfare model to account for trade-off between intelligence (‘bits’) and firepower (‘shots’). Intelligent targeting leads to aimed fire; absence of intelligence leads to unaimed fire, dependent on targets’ density. We propose a new Lanchester-type model that mixes aimed and unaimed fire, the balance between these being determined by quality of information. We...

Given the increasing importance of achieving low and stable inflation rate during the last decades, adopting the most suitable practices to implement monetary policies has always been of concern by monetary authorities of different countries. Inflation targeting (IT) regime is the most recent strategy to guide monetary policies that have been introduced following the occurrence of exchange rate...

This article presents the design strategy and implementation of a three-way Doherty power amplifier (DPA3W) to enhance efficiency at deep back-off. Theoretical equations are derived, based on which charts drawn explore available space, accounting for practical constraints related technology selected application. The proposed is demonstrated by design, fabrication experimental characterization m...

Integrase is actively studied as an antiviral target, but many inhibitors selected from biochemical screens fail to inhibit human immunodeficiency virus (HIV) replication or primarily affect off-site targets. Here we develop and validate a replication-competent, simian virus 40-HIV integrase mutant chimera as a novel tool to classify the mechanism of action of potential integrase inhibitors. Wh...

Experimentally restricting transgene expression exclusively to astrocytes has proven difficult. Using adeno-associated-virus-mediated gene transfer, we assessed two commonly used glial fibrillary acidic protein promoters: the full-length version gfa2 (2,210-bp human glial fibrillary acidic protein [GFAP] promoter) and the truncated variant gfaABC1D (681-bp GFAP promoter). The capacity to drive ...

Despite advances in controlled drug delivery, drug delivery systems (DDSs) with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled "off-on" DDS with...

The CRISPR/Cas9 system is a powerful genome editing tool and has been widely used for biomedical research. However, many challenges, such as off-target effects and lack of easy solutions for multiplex targeting, are still limiting its applications. To overcome these challenges, we first developed a highly efficient doxycycline-inducible Cas9-EGFP vector. This vector allowed us to track the cell...

Purpose To employ type II clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease to suppress ocular angiogenesis by genomic disruption of VEGF-A in human RPE cells. Methods CRISPR sequences targeting exon 1 of human VEGF-A were computationally identified based on predicted Cas9 on- and off-target probabilities. Single guide RNA (gRNA) cassettes with these target ...

the main purpose of this research has been to investigate whether inflation targeting improves macroeconomic performance as measured by the behavior of inflation, economic output and their variability among the countries employing inflation targeting. in this regard we have looked for empirical evidence in a world sample of 21 developed and developing inflation targeting countries before and af...